Tissue polypeptide antigen (TPA) was measured by radioimmunoassay in sera from 413 patients with various gynecologic tumors. The distribution of positive values (greater than 102 U/l) in the patients with gynecologic malignancies was such that the percentage of patients with elevated values appeared to increase with advancing stages of disease. Among the cervical cancer patients, elevated TPA values were observed in 11% of preinvasive, 35% of stage I and 67% of advanced cases. Similarly, the TPA values were elevated in 35% of the endometrial cancer patients. Among the patients with ovarian malignancies, serum TPA was elevated in 33% of borderline, 47% of stage I and 86% of advanced cases. However, serum TPA was elevated in 21% of patients with uterine myomas and in 12% of those with ovarian benign tumors. The serial measurements of TPA in sera of the patients with gynecologic malignancies showed that serum TPA levels correlated with the effect of treatment and the clinical courses. The present observations demonstrate that the lack of tumor specificity of TPA limits its diagnostic value in gynecologic malignancies but that serial measurements of this antigen appear to be useful for monitoring of patients.